Greenblum & Bernstein, P.L.C. PHARMA/BIOTECH NEWSLETTER Recent News in Intellectual Property
	October 2018
In This Issue: · CAFC finds Capoxone Dosage Obvious · Will the Patent Eligibility of Primer Pairs be Reconsidered by an en banc CAFC? Contact Us: Walter Schlapkohl, Ph.D., Esq. wschlapkohl@gbpatent.com 703-716-1191 (phone) 703-716-1180 (fax)	Obviousness of Capoxone Dosage Affirmed in Two CAFC Decisions -- by Thao Pham The US Court of Appeal for Federal Circuit (CAFC) has upheld two decisions, one by the United States District Court for the District of Delaware and another by the Patent Trial and Appeal Board, ruling that certain patents assigned to Yeda Research (“Yeda”) and Development Co., Ltd. and relating to Teva’s Capoxone drug are invalid as obvious. Copaxone is a medicine for treating the relapsing forms of multiple sclerosis. Teva’s Copaxone 20 mg/mL injected daily was approved by FDA. Patents covering a dosage regime of 40 mg/mL of Copaxone three times a week were licensed to Teva from Yeda. In 2015, Teva sued many companies, including Mylan, Sandoz and Amneal Pharmaceutical, in the District Court of Delaware, alleging of infringement of these patents as those companies had filed Abbreviated New Drug Application for the generic version of Copaxone 40 mg/mL administered 3 times per week. The District Court ruled that all asserted claims relating to dosage of Copaxone 40 mg/mL three times a week were invalid as obvious. According to the District Court, it was “obvious to try” to improve the treatment regime that previously required daily administration. Teva appealed against the District Court’s Judgement and argued that the District Court improperly relied on hindsight and that the court analyzed the obviousness of individual claim elements rather than the invention as a whole. However, the CAFC was not persuaded and affirmed the District Court’s judgement. In its opinion, the CAFC cited multiple earlier studies showing that administration of Copaxone three times a week would be more effective and cause fewer side effects than the daily lower dose of 20 mg/mL. Furthermore, the CAFC noted that there were only two amounts of Copaxone, 20mg/mL and 40 mg/ mL, which had been clinically tested as safe and effective. According to CAFC, decreasing the frequency of drug administration was desirable by the researchers at that time such that the dosage regime of 40 mg/mL three times weekly would have been obvious in the light of prior art. The cases are Teva Pharmaceuticals USA, Inc. v. Sandoz Inc., No. 17-1575 (Fed. Cir. Oct. 12, 2018) and Yeda Research and Development Co., v. Mylan Phamaceuticals Inc., Pharmaceuticals USA, Inc. v. Sandoz Inc., Nos. 17-1594, 17-1595, and 17-1596 (Fed. Cir. Oct. 12, 2018). Roche Molecular Sys., Inc. v. Cepheid -- by Christopher Wright In a recent decision by the CAFC (Roche Molecular Systems, Inc. v. Cepheid, No. 2017-1690 (Fed. Cir. Oct. 9, 2018)), the Federal Circuit took another look at the question of patentable subject-matter eligibility under 35 U.S.C. §101 for product claims to primers and method claims using primers for diagnostic testing. Primers are short nucleic acid molecules which are often fragments of larger, naturally occurring DNA sequences. Roche Molecular Systems, Inc. (Roche) identified eleven mutations in the rpoB gene of the pathogenic M. tuberculosis bacterium (MTB) and designed primers against each of these eleven mutations. The primers not only allow scientists to identify whether a biological sample contains MTB, but also predict whether the MTB strain is resistant to conventional antibiotic treatment. Roche then obtained a patent, U.S. Pat. No. 5,643,723 directed to, among other things, primers hybridizing to the MTB rpoB gene at one of the eleven naturally occurring mutations. Additionally the ‘723 Patent claimed a method for using the primers to diagnose the presence or absence of MTB. Roche sued Cepheid for patent infringement for their Xpert MTB/RIF Assay which can detect MTB in a biological sample including resistant MTB. In response, Cepheid filed a motion for summary judgment arguing that all of the claims of the ‘723 Patent were directed to patent-ineligible subject matter under 35 U.S.C. §101. The District Court of the Northern District of California granted summary judgement and invalidated the ‘723 Patent claims. Roche Molecular Systems, Inc. v. Cepheid, 2017 WL 6311568 (N.D. Cal., 2017). Roche then appealed the judgment to the Federal Circuit. On appeal, Roche argued that primers are man-made and are different from naturally occurring DNA by having a 3’ hydroxyl group, whereas MTB DNA does not contain a 3’ hydroxyl group or a 3’ end at all because bacterial DNA is circular. Roche, thus, attempted to distinguish the instant primer claims over the primer claims in In re BRCA1- & BRCA-2-Based Hereditary Cancer Test Patent Litig., 774 F.3d 755, 760 (Fed. Cir. 2014), which held that the genetic sequences of primers to eukaryotic organisms “are not distinguishable from the isolated DNA found patent-ineligible in Myriad” (citing Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 591 (2013)). In the holding, Judge Reyna and Judge Hughes dismissed these arguments. According to Judge Reyna, “except for the nucleotide sequences, the primers before us are not chemically or structurally different from the primers that were held patent-ineligible in BRCA1.” Judge Reyna further stated, “As this court determined in BRCA1, the subject matter eligibility inquiry of primer claims hinges on comparing a claimed primer to its corresponding DNA segment on the chromosome—not the whole chromosome.” From the standpoint of a practitioner, the Federal Circuit’s limited reasoning in Roche could open the door to arguments that small structural changes cannot suffice for the purposes of distinguishing compositions from products of nature under 35 U.S.C. §101. This decision may also underscore the benefits of claiming the amplicon as opposed to the primers themselves. Amplicons are the product of a PCR reaction using primers and, depending on the circumstance, may be distinguishable structurally from the DNA fragments upon which many primers are based. In a notable concurrence, Judge O’Malley agreed with Judges Reyna and Hughes that BRCA1 required a holding of patent ineligibility; however she also warned that the procedural context in BRCA1 (a motion for preliminary injunction) meant that the court reached a decision without all of the evidence necessary for a determination of invalidity and for this and other reasons, Judge O’Malley stated that the BRCA1 decision should be given a second look by an en banc court. With regard to the method claims, the Federal Circuit held that reciting a polymerase chain reaction was routine or conventional and, thus, could not add significantly more than what is recited in the product claim. Thus, method claims which feature using otherwise ineligible primers in a PCR reaction were also held to be directed to patent ineligible subject matter under 35 U.S.C. §101.